Chad Vanderbilt

Shengjia Chen, Gabriele Campanella, Abdulkadir Elmas et al.

Recent advances in artificial intelligence (AI), in particular self-supervised learning of foundation models (FMs), are revolutionizing medical imaging and computational pathology (CPath). A constant challenge in the analysis of digital Whole Slide Images (WSIs) is the problem of aggregating tens of thousands of tile-level image embeddings to a slide-level representation. Due to the prevalent use of datasets created for genomic research, such as TCGA, for method development, the performance of these techniques on diagnostic slides from clinical practice has been inadequately explored. This study conducts a thorough benchmarking analysis of ten slide-level aggregation techniques across nine clinically relevant tasks, including diagnostic assessment, biomarker classification, and outcome prediction. The results yield following key insights: (1) Embeddings derived from domain-specific (histological images) FMs outperform those from generic ImageNet-based models across aggregation methods. (2) Spatial-aware aggregators enhance the performance significantly when using ImageNet pre-trained models but not when using FMs. (3) No single model excels in all tasks and spatially-aware models do not show general superiority as it would be expected. These findings underscore the need for more adaptable and universally applicable aggregation techniques, guiding future research towards tools that better meet the evolving needs of clinical-AI in pathology. The code used in this work is available at \url{https://github.com/fuchs-lab-public/CPath_SABenchmark}.

Gabriele Campanella, Ricky Kwan, Eugene Fluder et al.

Recent breakthroughs in self-supervised learning have enabled the use of large unlabeled datasets to train visual foundation models that can generalize to a variety of downstream tasks. While this training paradigm is well suited for the medical domain where annotations are scarce, large-scale pre-training in the medical domain, and in particular pathology, has not been extensively studied. Previous work in self-supervised learning in pathology has leveraged smaller datasets for both pre-training and evaluating downstream performance. The aim of this project is to train the largest academic foundation model and benchmark the most prominent self-supervised learning algorithms by pre-training and evaluating downstream performance on large clinical pathology datasets. We collected the largest pathology dataset to date, consisting of over 3 billion images from over 423 thousand microscopy slides. We compared pre-training of visual transformer models using the masked autoencoder (MAE) and DINO algorithms. We evaluated performance on six clinically relevant tasks from three anatomic sites and two institutions: breast cancer detection, inflammatory bowel disease detection, breast cancer estrogen receptor prediction, lung adenocarcinoma EGFR mutation prediction, and lung cancer immunotherapy response prediction. Our results demonstrate that pre-training on pathology data is beneficial for downstream performance compared to pre-training on natural images. Additionally, the DINO algorithm achieved better generalization performance across all tasks tested. The presented results signify a phase change in computational pathology research, paving the way into a new era of more performant models based on large-scale, parallel pre-training at the billion-image scale.

Gabriele Campanella, Shengjia Chen, Ruchika Verma et al.

The use of self-supervised learning (SSL) to train pathology foundation models has increased substantially in the past few years. Notably, several models trained on large quantities of clinical data have been made publicly available in recent months. This will significantly enhance scientific research in computational pathology and help bridge the gap between research and clinical deployment. With the increase in availability of public foundation models of different sizes, trained using different algorithms on different datasets, it becomes important to establish a benchmark to compare the performance of such models on a variety of clinically relevant tasks spanning multiple organs and diseases. In this work, we present a collection of pathology datasets comprising clinical slides associated with clinically relevant endpoints including cancer diagnoses and a variety of biomarkers generated during standard hospital operation from two medical centers. We leverage these datasets to systematically assess the performance of public pathology foundation models and provide insights into best practices for training new foundation models and selecting appropriate pretrained models.

Gabriele Campanella, David Ho, Ida Häggström et al.

Lung cancer is the leading cause of cancer death worldwide, with lung adenocarcinoma being the most prevalent form of lung cancer. EGFR positive lung adenocarcinomas have been shown to have high response rates to TKI therapy, underlying the essential nature of molecular testing for lung cancers. Despite current guidelines consider testing necessary, a large portion of patients are not routinely profiled, resulting in millions of people not receiving the optimal treatment for their lung cancer. Sequencing is the gold standard for molecular testing of EGFR mutations, but it can take several weeks for results to come back, which is not ideal in a time constrained scenario. The development of alternative screening tools capable of detecting EGFR mutations quickly and cheaply while preserving tissue for sequencing could help reduce the amount of sub-optimally treated patients. We propose a multi-modal approach which integrates pathology images and clinical variables to predict EGFR mutational status achieving an AUC of 84% on the largest clinical cohort to date. Such a computational model could be deployed at large at little additional cost. Its clinical application could reduce the number of patients who receive sub-optimal treatments by 53.1% in China, and up to 96.6% in the US.

Yi Kan Wang, Ludmila Tydlitatova, Jeremy D. Kunz et al.

Molecular assays are standard of care for detecting genomic alterations in cancer prognosis and therapy selection but are costly, tissue-destructive and time-consuming. Artificial intelligence (AI) applied to routine hematoxylin and eosin (H&E)-stained whole slide images (WSIs) offers a fast and economical alternative for screening molecular biomarkers. We introduce OmniScreen, a high-throughput AI-based system leveraging Virchow2 embeddings extracted from 60,529 cancer patients with paired 489-gene MSK-IMPACT targeted biomarker panel and WSIs. Unlike conventional approaches that train separate models for each biomarker, OmniScreen employs a unified model to predict a broad range of clinically relevant biomarkers across cancers, including low-prevalence targets impractical to model individually. OmniScreen reliably identifies therapeutic targets and shared phenotypic features across common and rare tumors. We investigate the biomarker prediction probabilities and accuracies of OmniScreen in relation to tumor area, cohort size, histologic subtype alignment, and pathway-level morphological patterns. These findings underscore the potential of OmniScreen for routine clinical screening.

Chad Vanderbilt, Gabriele Campanella, Siddharth Singi et al.

Computational biomarkers (CBs) are histopathology-derived patterns extracted from hematoxylin-eosin (H&E) whole-slide images (WSIs) using artificial intelligence (AI) to predict therapeutic response or prognosis. Recently, slide-level multiple-instance learning (MIL) with pathology foundation models (PFMs) has become the standard baseline for CB development. While these methods have improved predictive performance, computational pathology lacks standardized intermediate data formats, provenance tracking, checkpointing conventions, and reproducible evaluation metrics required for clinical-grade deployment. We introduce GOLDMARK (https://artificialintelligencepathology.org), a standardized benchmarking framework built on a curated TCGA cohort with clinically actionable OncoKB level 1-3 biomarker labels. GOLDMARK releases structured intermediate representations, including tile coordinate maps, per-slide feature embeddings from canonical PFMs, quality-control metadata, predefined patient-level splits, trained slide-level models, and evaluation outputs. Models are trained on TCGA and evaluated on an independent MSKCC cohort with reciprocal testing. Across 33 tumor-biomarker tasks, mean AUROC was 0.689 (TCGA) and 0.630 (MSKCC). Restricting to the eight highest-performing tasks yielded mean AUROCs of 0.831 and 0.801, respectively. These tasks correspond to established morphologic-genomic associations (e.g., LGG IDH1, COAD MSI/BRAF, THCA BRAF/NRAS, BLCA FGFR3, UCEC PTEN) and showed the most stable cross-site performance. Differences between canonical encoders were modest relative to task-specific variability. GOLDMARK establishes a shared experimental substrate for computational pathology, enabling reproducible benchmarking and direct comparison of methods across datasets and models.

Gabriele Campanella, Eugene Fluder, Jennifer Zeng et al.

Artificial Intelligence (AI) has great potential to improve health outcomes by training systems on vast digitized clinical datasets. Computational Pathology, with its massive amounts of microscopy image data and impact on diagnostics and biomarkers, is at the forefront of this development. Gigapixel pathology slides pose a unique challenge due to their enormous size and are usually divided into tens of thousands of smaller tiles for analysis. This results in a discontinuity in the machine learning process by separating the training of tile-level encoders from slide-level aggregators and the need to adopt weakly supervised learning strategies. Training models from entire pathology slides end-to-end has been largely unexplored due to its computational challenges. To overcome this problem, we propose a novel approach to jointly train both a tile encoder and a slide-aggregator fully in memory and end-to-end at high-resolution, bridging the gap between input and slide-level supervision. While more computationally expensive, detailed quantitative validation shows promise for large-scale pre-training and fine-tuning of pathology foundation models.

Neeraj Kumar, Swaraj Nanda, Siddharth Singi et al.

Pathology foundation models (PFMs) have emerged as powerful tools for analyzing whole slide images (WSIs). However, adapting these pretrained PFMs for specific clinical tasks presents considerable challenges, primarily due to the availability of only weak (WSI-level) labels for gigapixel images, necessitating multiple instance learning (MIL) paradigm for effective WSI analysis. This paper proposes a novel approach for single-GPU \textbf{T}ask \textbf{A}daptation of \textbf{PFM}s (TAPFM) that uses vision transformer (\vit) attention for MIL aggregation while optimizing both for feature representations and attention weights. The proposed approach maintains separate computational graphs for MIL aggregator and the PFM to create stable training dynamics that align with downstream task objectives during end-to-end adaptation. Evaluated on mutation prediction tasks for bladder cancer and lung adenocarcinoma across institutional and TCGA cohorts, TAPFM consistently outperforms conventional approaches, with H-Optimus-0 (TAPFM) outperforming the benchmarks. TAPFM effectively handles multi-label classification of actionable mutations as well. Thus, TAPFM makes adaptation of powerful pre-trained PFMs practical on standard hardware for various clinical applications.